Down Syndrome Individuals Research Articles

Everyday Executive Functioning Profiles in Adults with Down Syndrome.

Research on everyday executive functions in individuals with Down Syndrome (DS) has focused mostly on children and adolescents. The current study examined everyday executive functions in DS adults. 27 DS adults (aged 22.00 to 42.00 years) were tested using the Behaviour Rating Inventory of Executive Function-Adult Informant Version (BRIEF-A). Findings revealed that DS adults exhibited greater impairments in Global Executive Composite (GEC), Working Memory, Plan/Organise, Task-Monitor and the Metacognition Index (MI) relative to typically developing adults in the normative sample. Substantial variabilities were found in all everyday executive function abilities among DS adults. Findings highlight the importance of making comprehensive assessments of everyday executive functions in DS individuals in order to identify problem areas and plan individualised support programmes.

Exploring the complex nexus of Alzheimers disease in down syndrome

In recent years, the life expectancy of individuals with Down Syndrome (DS) has increased significantly thanks to the advancements in healthcare and treatments, giving rise to an older population of people with DS. However, this demographic shift has brought about new concerns: as individuals with DS age, they face a higher incidence of early-onset Alzheimers Disease (EOAD) (i.e. the development of AD before the age of 65). Research has revealed an accelerated progression of symptoms, from onset of dementia to death, in DS patients. Thus, it is essential to identify the factors (both genetic and environmental) that underlie the development of different stages of AD-DS. Concomitantly, there is a pressing need to initiate intervention trials that could slow down or prevent the rapid advancement of AD-DS. This paper underscores the growing importance of addressing AD-DS in an ageing DS population. By elucidating genetic and environmental factors, clinical features, diagnostic challenges, roles of genes in the development of AD-DS, and potential future research directions, the article aims to contribute to a deeper understanding of dementia of the Alzheimer Type (DAT) and facilitate the development of effective treatments that could improve the lives of DS individuals affected by DAT.

Aging exacerbates oxidative stress and liver fibrosis in an animal model of Down Syndrome.

Down Syndrome (DS) is a common genetic disorder characterized by an extra copy of chromosome 21, leading to dysregulation of various metabolic pathways. Oxidative stress in DS is associated with neurodevelopmental defects, neuronal dysfunction, and a dementia onset resembling Alzheimer's disease. Additionally, chronic oxidative stress contributes to cardiovascular diseases and certain cancers prevalent in DS individuals. This study investigates the impact of ageing on oxidative stress and liver fibrosis using a DS murine model (Ts2Cje mice). Our results show that DS mice show increased liver oxidative stress and impaired antioxidant defenses, as evidenced by reduced glutathione levels and increased lipid peroxidation. Therefore, DS liver exhibits an altered inflammatory response and mitochondrial fitness as we showed by assaying the expression of HMOX1, CLPP, and the heat shock proteins Hsp90 and Hsp60. DS liver also displays dysregulated lipid metabolism, indicated by altered expression of PPARα, PPARγ, FATP5, and CTP2. Consistently, these changes might contribute to non-alcoholic fatty liver disease development, a condition characterized by liver fat accumulation. Consistently, histological analysis of DS liver reveals increased fibrosis and steatosis, as showed by Col1a1 increased expression, indicative of potential progression to liver cirrhosis. Therefore, our findings suggest an increased risk of liver pathologies in DS individuals, particularly when combined with the higher prevalence of obesity and metabolic dysfunctions in DS patients. These results shed a light on the liver's role in DS-associated pathologies and suggest potential therapeutic strategies targeting oxidative stress and lipid metabolism to prevent or mitigate liver-related complications in DS individuals.

The Impact of the COVID-19 Pandemic on Individuals with Down Syndrome: A Croatian Survey.

Severe acute respiratory syndrome coronavirus-2 infection has spread uncontrollably worldwide. Among the most vulnerable groups in society are populations with multiple comorbidities, including individuals with Down syndrome (DS). Our aim was to conduct an online survey to assess the impact of COVID-19 on DS individuals in Croatia. We also explored the views of their parents and caregivers about the challenges they faced during COVID-19. The anonymous online survey was launched in March 2022 and remained open until October 2022. Participants were conducted online through closed group on Facebook. The survey included questions about participant characteristics, medical information, clinical presentation of COVID-19, and challenges faced by the parents during COVID-19. A total of 268 surveys were collected and analysed. We found that age and body mass index of DS individuals were significantly and positively correlated with the clinical presentation of COVID-19. Lack of social activities, cancelled therapies, and psychological problems were the most frequently cited challenges during the pandemic. Clinicians and caregivers should primarily be alert to the same COVID-19 signs and symptoms that occur in the general population (fever, cough, shortness of breath). Ongoing therapies, social activities, and psychological support should be cited as indispensable for maintaining physical health and emotional well-being in DS individuals.

The Rapid Evaluation of Down Syndrome With Quantitative Fluorescence Polymerase Chain Reaction (QF-PCR): A Pilot Study Among the Population in Eastern Uttar Pradesh, India.

Background and objective Down syndrome (DS) is characterized by the presence of an additional chromosome; it is a typical chromosomal disorder causing intellectual disability in individuals. The diagnostic process for DS often involves conventional karyotyping, which can be time-consuming. Trisomy 21 and other chromosomal abnormalities may now be quickly and accurately diagnosed using quantitative fluorescence polymerase chain reaction (QF-PCR). In light of this, this study aimed to investigate chromosomal abnormalities in DS using conventional karyotyping and QF-PCR among thepopulation in easternUttar Pradesh, India. Methods Blood samples from 40individuals with clinically diagnosed DS were collected. Conventional karyotyping involved standard cytogenetic techniques, while QF-PCR utilized DNA extraction and analysis with chromosome-specific short tandem repeat (STR) markers. Results Various distinct physical characteristics were observed in the DS individuals, such as mongoloid slant and low-set ears. Karyotyping and QF-PCR analyses revealed different chromosomal configurations associated with DS trisomy 21, with additional chromosomal abnormalities found in some individuals, including partial monosomy 18 and mosaic trisomy 21. However, in a few cases, neither karyotyping nor QF-PCR revealed any abnormalities. Conclusions The study demonstrated that QF-PCR is a reliable and rapid method for diagnosing DS, providing results within 24 hours. This approach allows for the simultaneous diagnosis of a large number of samples and reduces the time required to obtain results. In the diagnostic procedure for DS, we believe QF-PCR will prove to be a usefultool. Furthermore, therapeutic interventions based on their clinical traits and molecular karyotyping can enhance the quality of life of people with DS.

Nutritional status and Mediterranean diet adherence of children with Down Syndrome and their siblings

Objectives This study aimed to investigate the nutritional status, eating practices, dietary intake, and dietary patterns of Down Syndrome (DS) individuals and their non-DS siblings. Methods This cross-sectional study was carried out with two groups, consisting of 34 DS individuals and 23 siblings. Socio-demographic data, anthropometric measurements, food consumption, and feeding difficulties were recorded. Dietary patterns are evaluated by the Mediterranean Diet Quality Index (KIDMED). The physical activity was measured with the Physical Activity Questionnaire for Older Children (PAQ-C). Results The rates of being overweight and obese were higher in the DS group according to the WHO BMI-z scores classification (p = 0.002). Even using Turkish DS-specific growth curves, being overweight and obese rates were higher (p = 0.041). No statistical difference was found in energy, macronutrient intake, and the mean KIDMED scores. However, most of the DS group had moderate adherence and most siblings had high adherence to the Mediterranean diet (p = 0.037). The PAQ-C scores were lower in the DS group (p = 0.039). Conclusions We conclude that DS individuals have higher rates of being overweight/obese even using DS-specific growth curves despite similar dietary patterns and nutrient intake. To prevent obesity in DS, it is important to evaluate their growth considering specific nutritional requirements.

Low TGF-β1 plasma levels are associated with cognitive decline in Down syndrome.

Almost all individuals with Down's syndrome (DS) show the characteristic neuropathological features of Alzheimer's disease (AD) by the age of 40, yet not every individual with DS experiences symptoms of AD later in life. Similar to neurotypical developing subjects, AD in people with DS lasts for a long preclinical phase in which biomarkers follow a predictable order of changes. Hence, a prolonged asymptomatic period precedes the onset of dementia, underscoring the importance of identifying new biomarkers for the early detection and monitoring of cognitive decline in individuals with DS. Blood-based biomarkers may offer an alternative non-invasive strategy for the detection of peripheral biological alterations paralleling nervous system pathology in an early phase of the AD continuum. In the last few years, a strong neurobiological link has been demonstrated between the deficit of transforming growth factor-β1 (TGF-β1) levels, an anti-inflammatory cytokine endowed with neuroprotective activity, and early pro-inflammatory processes in the AD brain. In this clinical prospective observational study, we found significant lower plasma TGF-β1 concentrations at the first neuropsychological evaluation (baseline = T0) both in young adult DS individuals (19-35years) and older DS subjects without AD (35-60years) compared to age- and sex-matched healthy controls. Interestingly, we found that the lower TGF-β1 plasma concentrations at T0 were strongly correlated with the following cognitive decline at 12 months. In addition, in young individuals with DS, we found, for the first time, a negative correlation between low TGF-β1 concentrations and high TNF-α plasma concentrations, a pro-inflammatory cytokine that is known to be associated with cognitive impairment in DS individuals with AD. Finally, adopting an ex vivo approach, we found that TGF-β1 concentrations were reduced in parallel both in the plasma and in the peripheral blood mononuclear cells (PBMCs) of DS subjects, and interestingly, therapeutic concentrations of fluoxetine (FLX) applied to cultured PBMCs (1µM for 24h) were able to rescue TGF-β1 concentrations in the culture media from DS PBMCs, suggesting that FLX, a selective serotonin reuptake inhibitor (SSRI) endowed with neuroprotective activity, might rescue TGF-β1 concentrations in DS subjects at higher risk to develop cognitive decline.

Differentiation of the body build and posture in the population of people with intellectual disabilities and Down Syndrome: a systematic review

BackgroundThe aim of the study was to identify the variables of the internal compensatory mechanisms that differentiate the body build and posture of people with Down syndrome (DS) from the intellectual disability (ID) population. It was assumed that gaining knowledge in the abovementioned aspect will allow for a better understanding of the limitation of the kinesthetic abilities of people with ID and DS and simultaneously enable to optimize the process of planning and interventions to improve physical activity in this population with the adequate use of theirs strengths in the biomechanical and morphofunctional systems.MethodsThe methodology of this systematic review was developed according to the PRISMA guidelines. A search of PubMed, EBSCO, Scopus databases was conducted to identify all studies on DS/ID and the body build and posture from 2003 to 2023.Results395 articles were assessed to determine eligibility, while 22 studies met the inclusion criteria and were subjected to detailed analysis and assessment of their methodological quality. The differentiation of the body build and posture in DS population can be induced by both internal and external compensatory mechanisms. It is difficult to confirm the direct effect of the intrinsic variables that impact the body build and posture in the ID population, excluding people with DS.ConclusionsCompared to other ID, the intrinsic differences in the body build and posture in DS individuals were induced by gender, age, and level of ID. The tendency for diversity between DS and other ID populations in body build and posture may be determined by the presence of the third copy of chromosome 21 in DS group. Internal compensatory processes may be induced mainly by abnormalities in the structure of the cervical vertebrae and feet. IQ should not be used as the only variable that identifies the population of people with ID.

Phenotyping Down syndrome: discovery and predictive modelling with electronic medical records.

Individuals with Down syndrome (DS) have a heightened risk for various co-occurring health conditions, including congenital heart disease (CHD). In this two-part study, electronic medical records (EMRs) were leveraged to examine co-occurring health conditions among individuals with DS (Study 1) and to investigate health conditions linked to surgical intervention among DS cases with CHD (Study 2). De-identified EMRs were acquired from Vanderbilt University Medical Center and facilitated creating a cohort of N=2282 DS cases (55% females), along with comparison groups for each study. In Study 1, DS cases were one-by-two sex and age matched with samples of case-controls and of individuals with other intellectual and developmental difficulties (IDDs). The phenome-disease association study (PheDAS) strategy was employed to reveal co-occurring health conditions in DS versus comparison groups, which were then ranked for how often they are discussed in relation to DS using the PubMed database and Novelty Finding Index. In Study 2, a subset of DS individuals with CHD [N=1098 (48%)] were identified to create longitudinal data for N=204 cases with surgical intervention (19%) versus 204 case-controls. Data were included in predictive models and assessed which model-based health conditions, when more prevalent, would increase the likelihood of surgical intervention. In Study 1, relative to case-controls and those with other IDDs, co-occurring health conditions among individuals with DS were confirmed to include heart failure, pulmonary heart disease, atrioventricular block, heart transplant/surgery and primary pulmonary hypertension (circulatory); hypothyroidism (endocrine/metabolic); and speech and language disorder and Alzheimer's disease (neurological/mental). Findings also revealed more versus less prevalent co-occurring health conditions in individuals with DS when comparing with those with other IDDs. Findings with high Novelty Finding Index were abnormal electrocardiogram, non-rheumatic aortic valve disorders and heart failure (circulatory); acid-base balance disorder (endocrine/metabolism); and abnormal blood chemistry (symptoms). In Study 2, the predictive models revealed that among individuals with DS and CHD, presence of health conditions such as congestive heart failure (circulatory), valvular heart disease and cardiac shunt (congenital), and pleural effusion and pulmonary collapse (respiratory) were associated with increased likelihood of surgical intervention. Research efforts using EMRs and rigorous statistical methods could shed light on the complexity in health profile among individuals with DS and other IDDs and motivate precision-care development.

Comparison between DSQIID total/sub‐item scores and plasma p‐tau elevation in adults with Down syndrome

AbstractBackgroundPeople with Down syndrome (DS) are at a high risk of developing Alzheimer’s disease (AD) with aging. The Dementia Screening Questionnaire for Individuals with Intellectual Disabilities (DSQIID) is an appropriate screening tool for detecting dementia in DS. However, it remains unclear whether this questionnaire genuinely reflects the neuropsychiatric signs of DS‐AD with biomarker‐based diagnoses.MethodTo validate the usefulness of DSQIID for detecting DS‐AD, we conducted this cross‐sectional observational study comparing plasma tau phosphorylated at the threonine 181 residue (p‐tau) level of a representative AD biomarker to the total score and each sub‐item score of the DSQIID. Plasma p‐tau levels and apolipoprotein E (ApoE) types were determined in 56 individuals with DS. Among these patients, 43 completed the DSQIID. Thirty‐three controls were enrolled to set the reference value for plasma p‐tau levels.ResultsThe plasma p‐tau level in the DS group was age‐dependently elevated and reached an abnormal cut‐off over the age of 40 years. Age‐related elevation of p‐tau level was steeper in DS individuals with the ApoE4 allele than in those without ApoE4, validating the usefulness of plasma p‐tau as a surrogate indicator of AD‐DS development. In contrast, although DSQIID total and some sub‐item scores were positively correlated with plasma p‐tau level, all these significant correlations disappeared after age adjustment. Moreover, two sub‐items, “Talks to self” and “Generally appears more forgetful,” were significantly negatively correlated with plasma p‐tau level after age‐adjustment.ConclusionThese results suggest that there is room for improvement in DSQIID for detecting DS‐AD.

NFL and pTau species from plasma neuronal and astrocyte exosomes correlate with neuropathological development and neurodegeneration in Down Syndrome

AbstractBackgroundIndividuals with Down Syndrome (DS) develop Alzheimer’s disease (AD). Plasma Neurofilament (NFL), phospho tau181, and 231 (pTau181 and 231) are currently considered promising blood‐based biomarkers of brain tau pathology in AD. However, it is still unknown whether the use of exosomal NFL and different pTau epitopes offers overlapping or complementary information about tau pathology information in this population. Using biobanked DSBI plasma samples, we aimed to understand the relationship between blood‐based exosome derived NFL, pTau181 and 231 with age, brain amyloid and tau pathology, APOE status, as well as cognitive and functional performance in non‐demented DS individuals. We hypothesized that the relationship between NFL, pTau‐181, and 231 derived from plasma neuronal and astrocyte exosomes (NDEs/ADEs) with that of other fluid and imaging biomarkers might help to accurately assess brain AD pathology in DS adults.MethodExosomes were isolated from the plasma of adult DS individuals who were enrolled in DSBI. Exosomes were precipitated and isolated using an ExoQuick kit. Isolated exosomes were enriched for NDEs and ADEs using antibodies against neuronal (L1CAM) and astrocyte (GLAST), respectively, followed by magnetic immunocapture and fluorescence‐activated cell sorting. NDEs and ADEs were assessed for their size and marker proteins by Nanosight, electron microscopy, and ELISA. NFL was quantified by SIMOA assays, while pTau epitopes 181 and 231 were quantified by MSD assays in NDEs and ADEs. We compared the diagnostic accuracy of exosomal p‐tau epitopes with NFL levels. We analyzed imaging data and cognitive measures in relation to NFL, pTau181, and pTau231 of NDEs and ADEs in adults with DS.ResultBlood‐based NDEs and ADEs showed expected exosomal size, shape, and distribution. ELISA showed the presence of exosome marker proteins on NDEs and ADEs. The p‐tau epitopes showed correlations with each other. We showed significant correlations of exosomal NFL and pTau epitopes with age, brain amyloid, tau pathology, APOE status, and cognitive and functional performance.ConclusionThe correlations reported here lay a foundation to study the use of plasma‐derived exosomal NFL and pTau181, and pTau231 as a “combination biomarker” in clinical trials and to better understand the neurodegenerative trajectories in DSAD.

Electrophysiological effects of mitochondria‐derived extracellular vesicles: implications for memory dysfunction in neurodegenerative disorders

AbstractBackgroundMitovesicles are a newly identified subtype of small extracellular vesicles (EVs) of mitochondrial origin. We recently developed a method to separate mitovesicles from other EVs after their isolation from the extracellular space of murine and human brain tissues. This method permits the study of the roles of mitovesicles in physiology and disease.Given their origin, we hypothesized that mitochondrial dysfunction, a hallmark of both Alzheimer’s disease (AD) and Down syndrome (DS), could induce alterations in mitovesicles, thus perturbing brain homeostasis and contributing to propagation of pathology. Therefore, we studied mitovesicle components and functionality after their isolation from the brain of a mouse model of DS (hereafter Ts2) as compared to diploid (2N) controls, as well as from frontal cortices of individuals with DS as compared to their age‐matched 2N controls.MethodBrain mitovesicles were isolated and analyzed by Western blotting, electron microscopy, nanotrack analysis, and monoamine neurotransmitter degradation assay as recently described (D’Acunzo, et al., 2022, PMID: 35962195). Coronal hippocampal slices from wild‐type mice were perfused with different subtypes of brain EVs, pretreated or not with clorgiline and pargyline (1 μM each), irreversible inhibitors of the monoamine oxidases type A and B (MAO‐A and MAO‐B), respectively. Long‐term potentiation (LTP) was induced at the level of the Schaeffer collateral fibers through a theta‐burst stimulation (Fà, et al., 2014, PMID: 24643165).ResultMitovesicle number is higher in brains of DS individuals and of Ts2 mice and contain a higher MAO‐B protein amount and enzymatic activity as compared to diploid controls, suggesting a potential mitovesicle‐dependent impairment of neuroamine homeostasis in DS. In agreement with that, Ts2 (but not 2N) mitovesicles stimulated a decreased LTP in recipient hippocampal slices as compared to vehicle control (Fig. 1; mtVs: mitovesicles). This biological activity was abolished when MAO‐B (but not MAO‐A) was blocked. The other EV subtypes of both genotypes, microvesicles and exosomes, did not trigger an effect on LTP. DS changes were found to be sex independent.ConclusionPathogenic mitovesicles are previously undescribed active players of the brain extracellular milieu by regulating LTP via MAO‐B, and potentially contribute to memory formation deficiencies typically found in AD and DS.

Alzheimer's polygenic risk scores are associated with cognitive phenotypes in Down syndrome.

This study aimed to investigate the influence of the overall Alzheimer's disease (AD) genetic architecture on Down syndrome (DS) status, cognitive measures, and cerebrospinal fluid (CSF) biomarkers. AD polygenic risk scores (PRS) were tested for association with DS-related traits. The AD risk PRS was associated with disease status in several cohorts of sporadic late- and early-onset and familial late-onset AD, but not in familial early-onset AD or DS. On the other hand, lower DS Mental Status Examination memory scores were associated with higher PRS, independent of intellectual disability and APOE (PRS including APOE, PRSAPOE , p=2.84×10-4 ; PRS excluding APOE, PRSnonAPOE , p=1.60×10-2 ). PRSAPOE exhibited significant associations with Aβ42, tTau, pTau, and Aβ42/40 ratio in DS. These data indicate that the AD genetic architecture influences cognitive and CSF phenotypes in DS adults, supporting common pathways that influence memory decline in both traits. Examination of the polygenic risk of AD in DS presented here is the first of its kind. AD PRS influences memory aspects in DS individuals, independently of APOE genotype. These results point to an overlap between the genes and pathways that leads to AD and those that influence dementia and memory decline in the DS population. APOE ε4 is linked to DS cognitive decline, expanding cognitive insights in adults.

Epigenomic signature of major congenital heart defects in newborns with Down syndrome

BackgroundCongenital heart defects (CHDs) affect approximately half of individuals with Down syndrome (DS), but the molecular reasons for incomplete penetrance are unknown. Previous studies have largely focused on identifying genetic risk factors associated with CHDs in individuals with DS, but comprehensive studies of the contribution of epigenetic marks are lacking. We aimed to identify and characterize DNA methylation differences from newborn dried blood spots (NDBS) of DS individuals with major CHDs compared to DS individuals without CHDs.MethodsWe used the Illumina EPIC array and whole-genome bisulfite sequencing (WGBS) to quantitate DNA methylation for 86 NDBS samples from the California Biobank Program: (1) 45 DS-CHD (27 female, 18 male) and (2) 41 DS non-CHD (27 female, 14 male). We analyzed global CpG methylation and identified differentially methylated regions (DMRs) in DS-CHD versus DS non-CHD comparisons (both sex-combined and sex-stratified) corrected for sex, age of blood collection, and cell-type proportions. CHD DMRs were analyzed for enrichment in CpG and genic contexts, chromatin states, and histone modifications by genomic coordinates and for gene ontology enrichment by gene mapping. DMRs were also tested in a replication dataset and compared to methylation levels in DS versus typical development (TD) WGBS NDBS samples.ResultsWe found global CpG hypomethylation in DS-CHD males compared to DS non-CHD males, which was attributable to elevated levels of nucleated red blood cells and not seen in females. At a regional level, we identified 58, 341, and 3938 CHD-associated DMRs in the Sex Combined, Females Only, and Males Only groups, respectively, and used machine learning algorithms to select 19 Males Only loci that could distinguish CHD from non-CHD. DMRs in all comparisons were enriched for gene exons, CpG islands, and bivalent chromatin and mapped to genes enriched for terms related to cardiac and immune functions. Lastly, a greater percentage of CHD-associated DMRs than background regions were differentially methylated in DS versus TD samples.ConclusionsA sex-specific signature of DNA methylation was detected in NDBS of DS-CHD compared to DS non-CHD individuals. This supports the hypothesis that epigenetics can reflect the variability of phenotypes in DS, particularly CHDs.

Prevalence of Malocclusions in Down Syndrome Population: A Cross-Sectional Study.

Background and Objectives: A higher prevalence of dental malocclusion has been suggested among individuals with Down Syndrome (DS) compared to controls, although no studies to date have investigated such a difference according to age group. Therefore, the aim of this study was to compare the prevalence of dental malocclusion and other orthodontic measures between DS and non-syndromic (non-DS) individuals across three age groups of children, adolescents, and adults. Materials and Methods: This cross-sectional study was conducted on a total of 147 patients. Of those, 72 were diagnosed with DS and were divided into N = 15 children (<10 years), N = 23 adolescents (10-18 years) and N = 34 adults (>18 years). The remaining 75 patients were sex- and age-matched controls. The two groups were compared according to age group in terms of the prevalence of dental malocclusion, measures of sagittal, vertical, and transverse discrepancy, facial profile, and probable sleep bruxism with chi-square tests for proportion. Results: The DS patients consistently exhibited a higher prevalence of Class 3 malocclusion, concave profile and anterior crossbite compared to the non-DS patients, regardless of age group. The non-DS adolescents presented with a significantly higher prevalence of convex profile than the DS adolescents. The adolescent and adult DS patients most commonly presented with a maxillary transverse discrepancy and posterior crossbite compared to the non-DS controls. The DS adults had a higher prevalence of probable sleep bruxism. Conclusions: Patients with DS showed a higher prevalence of Class 3 malocclusion, concave profile and anterior crossbite compared to non-DS controls, regardless of age group. Other orthodontic measures showed a fluctuation according to the age group considered.

DNA methylation profiling in Trisomy 21 females with and without breast cancer.

Down Syndrome (DS) is the most common chromosome anomaly in humans and occurs due to an extra copy of chromosome 21. The malignancy profile in DS is unique, since DS patients have a low risk of developing solid tumors such as breast cancer however they are at higher risk of developing acute myeloid leukemia and acute lymphoblastic leukemia. In this study, we investigated DNA methylation signatures and epigenetic aging in DS individuals with and without breast cancer. We analyzed DNA methylation patterns in Trisomy 21 (T21) individuals without breast cancer (T21-BCF) and DS individuals with breast cancer (T21-BC), using the Infinium Methylation EPIC BeadChip array. Our results revealed several differentially methylated sites and regions in the T21-BC patients that were associated with changes in gene expression. The differentially methylated CpG sites were enriched for processes related to serine-type peptidase activity, epithelial cell development, GTPase activity, bicellular tight junction, Ras protein signal transduction, etc. On the other hand, the epigenetic age acceleration analysis showed no difference between T21-BC and T21-BCF patients. This is the first study to investigate DNA methylation changes in Down syndrome women with and without breast cancer and it could help shed light on factors that protect against breast cancer in DS.

Analysis of Heart Rate, Perception of Physical Effort and Performance of Individuals with Down Syndrome Submitted to a Protocol of Virtual Games for Home-Based Telerehabilitation

Down syndrome (DS) is a genetic condition associated with impairments in several body systems, which may negatively influence the habit of practicing physical activities (PAs), increasing sedentary habits and the risk of comorbidities. Additionally, difficulty in accessing services, financial limitations and lack of interest may interfere with the practice of PAs. Considering the necessity of developing effective treatment alternatives, to increase the possibility of access and the interest of participants, we conducted a study using telerehabilitation with a virtual task to promote PA and analyze the motor performance of DS individuals. Our protocol consisted of 11 sessions of the virtual game called MoveHero. A total of 34 individuals with DS and 34 individuals with typical development participated in the study. Heart rate (HR) and rating of perceived effort (RPE) were collected at rest and during the game. Our results show that virtual reality presents a great possibility to promote PA and a way out of a sedentary lifestyle for DS individuals, considering the enhancement in HR and RPE found during the protocol for both groups. Moreover, our results show positive outcomes regarding motor performance, with significant improvement in the task with practice, demonstrating that individuals with DS are able to improve their motor proficiency with adequate stimuli in the virtual environment.

Association of Down syndrome with periodontal diseases: Systematic review and meta-analysis.

Down syndrome (DS) is distinguished by cognitive disability, a concave profile, and systemic complications. Oral diseases have been reported to be common in DS patients. To investigate the association between DS and periodontal diseases. Two independent reviewers searched six bibliographic databases up to January 2023 and used additional search methods to identify published studies on gingivitis or periodontitis in people with and without DS. Meta-analysis, risk of bias, sensibility analysis, publication bias, and evidence grading were all carried out. Twenty-six studies were included for analysis. There was a tendency for increased plaque accumulation, periodontal probing, periodontal attachment level, bleeding on probing and indices in DS individuals. Meta-analysis of 11 studies showed a significant association between DS and periodontitis (OR 3.93; 95% CI 1.81-8.53). Probing depth was significantly high in individuals with DS as compared to controls (mean difference 0.40mm; 95% CI 0.09-0.70). Gingivitis was significantly associated (OR 1.93; 95% CI 1.09-3.41) with DS in four studies. The evidence was classified as 'moderate certainty'. Medium/low-quality studies demonstrate that Down syndrome is strongly associated with periodontitis and moderately associated with gingivitis.

Sleep and behavioral problems in Down syndrome: differences between school age and adolescence.

Individuals with Down syndrome (DS) are at risk of developing sleep problems. In spite of the well-established knowledge on the presence of sleep difficulties in DS individuals and the associated emotional and behavioral problems, less is known about the possible differences in the kind of associations between sleep and emotional/behavioral problems across different age ranges. In this retrospective study, we included 289 participants with DS aged 6-18 years with the aims to explore differences in the distribution of sleep problems between specific age groups (school age vs. adolescence) and to identify specific age-based associations between sleep problems and emotional/behavioral problems. Some differences in the distribution of sleep problems have emerged between age groups. Moreover, differences in the patterns of association between emotional/behavioral difficulties and sleep problems-in particular, sleep-related breathing difficulties and parasomnias-have been observed. However, sleep-wake transition disorders and excessive daily somnolence appear to be related to emotional and behavioral problems (both internalizing and externalizing), in general, across school age and adolescence. These results remark the importance of appropriate neuropsychiatric and psychological evaluation taking into account the age-specific needs and features of individuals with DS.

Sleep Disorder Prevalence among Brazilian Children and Adolescents with Down Syndrome: An Observational Study

Background: Down syndrome (DS) is the most common chromosomal disorder and is related to congenital heart disease, sleep disorders and obesity. Sleep problems are common in DS children, including obstructive sleep apnea. This study aimed to investigate the prevalence of sleep disorders in a group of 41 DS children and adolescents, by two validated questionnaires. Methods: This is a qualitative observational study. The guardians of DS individuals (1–17 years old) answered two questionnaires (sleep questionnaire by Reimão and Lefévre–QRL and sleep disorders scale for children–SDSC) using the Google forms tool. Results: Most DS children wake up at least once during the night (68.28%), sleep during the day (56%) and fall asleep within 15 to 30 min (36.58%), urinate in the sleep at night (53.65%), move around a lot while sleeping at night (78.04) and snore at night (53.66%). In SDSC, 36.59% (n = 15) have some sleep disorder and 29.3% (n = 12) have sleep-disordered breathing. Conclusions: The DS children and adolescents present sleep-compromising factors. Moreover, obstructive sleep apnea is the most prevalent sleep-disordered breathing. Considering the findings of the current study, Google forms is an important tool to evaluate the sleep disorders of DS children and adolescents.